Evolutionary models of drug use seek to explain human drug usage from the perspective of evolutionary fitness. Plants, for instance, may provide fitness benefits by relieving pain. Proponents of this model of drug use suggest that the consumption of pharmacological substances for medicinal purposes evolved in the backdrop of human–plant coevolution as a means of self-medication. Humans thus learned to ignore the cues of plant toxicity (e.g., bitter taste) because ingesting the bioactive compounds of plants in small amounts was therapeutic.

The hijack model of substance addiction suggests that psychoactive drugs act on ancient and evolutionarily conserved neural mechanisms associated with positive emotions that evolved to mediate incentive behavior. They induce emotions that in human evolutionary history signaled a benefit for the group. Modern drugs tap into these emotions without passing on any evolutionary advantage. This may explain the modern problems of overuse and addiction.

Hijack hypothesis

The dominant paradigm of drug abuse focuses on human neurobiology and suggests that drug use is the result of reward-related behavior and that drug addiction is a consequence of drug interference with natural reward systems. Specifically, this tradition postulates that the chemical compounds humans seek out increase brain dopamine levels and thereby effectively usurp the mesolimbic pathway, a system originally intended to motivate/reward fitness enhancing behaviors such as those that increase access to food and sex.

From an evolutionary psychiatry viewpoint, susceptibility to addictive behaviours may be understood as a byproduct of neural circuits evolved for reward-seeking in ancestral environments—modern psychoactive substances then "hijack" those circuits in maladaptive ways.

History Ideas concerning the neural bases of motivation and reinforcement in behavior can be traced back to the 1950s. In 1953, Olds and Milner published findings implicating a brain region, specifically a cluster of dopamine neurons, with reward-based learning. Addictive substances were later discovered to increase dopamine in the region of the brain associated with reward-based-learning (see: brain stimulation reward).

Proximate mechanisms

Molecular pathways Research on the molecular pathways of addiction suggests that addictive substances, despite their diverse chemical substrates, converge on a common circuitry in the brain's limbic system. Specifically, drugs are thought to activate the mesolimbic dopamine pathway, facilitating dopamine transmission in the nucleus accumbens, via disinhibition, excitation, uptake blockade, etc. to produce a dopamine-like, yet dopamine independent effect.

Emotional pathways The hijack model of substance addiction explains that drugs that elicit positive emotion mediate incentive motivation in the nucleus accumbens of the brain. Put another way, addictive substances act on ancient and evolutionarily conserved neural mechanisms associated with positive emotions that evolved to mediate incentive behavior. Psychoactive drugs induce emotions that in human evolutionary history signaled increases in fitness. Positive emotions such as euphoria and excitation are tools chosen by natural selection to help direct the behavior and physiology of an individual towards an increase in Darwinian fitness. For example, in the environment of evolutionary adaptation, humans would feel positive euphoric emotions in response to a successful foraging session or in the event of a successful breeding. Many psychoactive substances provide this same feeling and yet do not produce fitness benefits.

Researchers have shown how emotional disposition is correlated with problematic use of alcohol, wherein if the reason for alcohol consumption is positive, the user is thought to drink to enhance positive feelings with greater control of the substance than if the user's emotional disposition prior to alcoholic consumption was negative. In these cases, the individual is drinking to cope and is shown to have less control over his/her own use. Alcohol mediates negative feelings by their suppression but also encourages the habituated continuance of positive emotion. Recovering alcoholics often report that the reason for relapse is often related to the impulse to compensate for negative feelings, resulting in a motivation to cope and therefore drink.

Evolutionary mismatch Drugs such as nicotine, cocaine, alcohol, tetrahydrocannabinol, and opium artificially stimulate the emotions and neural circuits involved in the mesolimbic reward system, thus encouraging drug consumption despite any negative side-effects. The hijack hypothesis suggests that drugs are effective hijackers of neural reward circuitry (e.g. the mesolimbic dopamine system) because they are evolutionarily novel. Specifically proposing that modern-day drug concentrations, methods of delivery, and the existence of certain drugs themselves were not available until recently on an evolutionary time scale, and thus human biology has been slow to adapt and is presently mismatched and susceptible.

To explain how drugs increase dopamine and cause positive emotions while at the same time lowering reproductive fitness, researchers posited that evolutionarily novel drugs hijack the brain's mesolimbic dopamine system and generate a false positive signal of a fitness benefit as well as inhibiting negative effects, to signal a lack of negative fitness consequences. Modern drug addiction fundamentally indicates a false increase of fitness, leading to increasing substance addiction to continue gain, even if the gain is realized as being false. That these drugs create a signal in the brain that indicates, falsely, the arrival of a huge fitness benefit which changes behavioral propensities so that drug-seeking increases in frequency and displaces adaptive behaviors. Proponents of the hijack hypothesis suggest that the paradox of drug reward is due to this evolutionary mismatch, that extant access to psychoactive drug concentrations and products are unmatched by those that existed in the past.

The paradox of drug reward

Why do humans seek out and consume drugs that harm them? The paradox of drug reward refers to the puzzling ability of drugs to induce both aversive and rewarding effects. Despite contention on the particulars of dopamine-induced reward and behavior, there is agreement that dopamine plays an instrumental role in the processing of reward-related stimuli and that drug-induced dopamine stimulation explains at least some part of substance use phenomena. And still, almost all major recreational drugs are plant secondary metabolites or a close chemical analog. The secondary plant compounds from which psychoactive drugs are derived are a form of interspecies defense chemicals that evolved to deter and/or mitigate consumption of the plant soma by herbivores/insects. The compounds from which psychoactive drugs are derived evolved to punish herbivore consumption, not reward it.

Human-plant co-evolutionary history Animals evolved to exploit plant tissues and energy stores and in response, plants developed a number of defenses, including neurotoxins. The presence and concentration of these toxins vary by plant tissue, with leaves and organs central to reproduction and energy conservation displaying high toxin concentrations (e.g. pistils/stamens and storage organs) and absent in tissue central to seed dispersion (e.g. fruit). The power and effectiveness of plant neurotoxic substances has been shaped by ~400 million years of evolution. Plant-derived neurotoxins are not evolutionarily novel and human neurophysiology recognizes plant toxins and activates specialized xenobiotic defenses that involve genes, tissue barriers, neural circuits, organ systems, and behaviors to protect against them.

Herbivore defense mechanisms Drug toxicity and aversion exist in humans and are at odds with the theory of drug reward. Chronic drug use is harmful in humans and the human brain has evolved defenses to prevent, not reinforce substance use. In response to the evolution of plant chemical defenses, herbivores have co-evolved a number of countermeasures, including (1) compounds that prevent or attenuate induction of plant chemical defenses; (2) detoxification mechanisms, including enzymes and symbiotic relationships with microbes to detoxify or extract nutrients from plant defenses, and cellular membrane carrier proteins for toxin transport; and (3) chemosensors and aversive learning mechanisms that permit selective feeding on less toxic tissues.

Human defense mechanisms Human and plant neurotoxin coevolution is evidenced by features of the xenobiotic defense network. Tobacco activates defense mechanisms which researchers suggests it is recognized as toxic not a reward. Nicotine activates bitter taste receptors in the mouth and gut. Ingesting 4–8 mg of nicotine causes burning of the mouth and throat, nausea, aversion, vomiting and diarrhea. In higher doses the effects are more robust and can result in weakness, confusion, dizziness, convulsions, and coma. If consumed in high enough amounts, acute nicotine toxicity can trigger failure of the respiratory system and induce death in human adults within minutes. First-time users of tobacco especially report a variety of unpleasant effects upon administration of nicotine, including nausea, vomiting, gastrointestinal distress, headache, and sweating. This, when taken with the fact that nicotine is a plant toxin that evolved to deter herbivores, suggests instead that the human body naturally recognizes tobacco as a toxic substance, and not a reward.

In addition, research has found genetic evidence that humans have had a long evolutionary history to plant neurotoxins. Sullivan et al. (2008) has noted that humans, like other mammals, have 'inherited' the cytochrome P450 system, which functions to detoxify chemicals found in the environment, including plant neurotoxins. The ubiquity of CYP genes in humans worldwide, including CYP2A6 and CYP2B6, which metabolize nicotine, as well as other drugs, might suggest an evolutionary history with humans and plant neurotoxins. The mammalian body has also evolved to develop defenses against over toxicity, such as exogenous substance metabolism and vomiting reflexes.

Neurotoxin regulation hypothesis

The neurotoxin regulation model of human drug use proposes that during the course of human evolution, plant consumption played a key role. The hypothesis suggests that the compulsory consumption of both the nutrients and neurotoxins in plants selected for a system capable of maximizing the benefits of plant energy extraction while mitigating the cost of plant toxicity. To do this, humans evolved a defense system in which plant consumption is mediated by cues of toxicity in a manner sensitive to the individual's toxicity threshold, maintaining blood toxin concentrations below a critical level.

Evidence for toxin regulation Research on herbivores supports the notion of a regulation pathway. Plant toxin concentration informs mammalian herbivore food choices, with herbivores moderating toxicity by capping daily plant intake to accommodate blood toxin concentrations. This mechanism exists across herbivore species and remains static in response to a range of plant toxins, even those that are evolutionarily novel. Similarly, in laboratory conditions, mice have been shown to moderate administration of drugs regardless of dose per injection or the number of lever presses required.

Example: Nicotine